Inherited human ITK deficiency impairs IFN-γ immunity and underlies tuberculosis

ABSTRACT: Inborn errors of IFN-γ immunity can underlie tuberculosis (TB). We report three patients from two kindreds without EBV viremia or disease but with severe TB and inherited complete ITK deficiency, a condition associated with severe EBV disease that renders immunological studies challenging. They have CD4+ αβ T lymphocytopenia with a concomitant expansion of CD4-CD8- double-negative (DN) αβ and Vδ2- γδ T lymphocytes, both displaying a unique CD38+CD45RA+T-bet+EOMES- phenotype. Itk-deficient mice recapitulated an expansion of the γδ T and DN αβ T lymphocyte populations in the thymus and spleen, respectively. Moreover, the patients' T lymphocytes secrete small amounts of IFN-γ in response to TCR crosslinking, mitogens, or forced synapse formation with autologous B lymphocytes. Finally, the patients' total lymphocytes secrete small amounts of IFN-γ, and CD4+, CD8+, DN αβ T, Vδ2+ γδ T, and MAIT cells display impaired IFN-γ production in response to BCG. Inherited ITK deficiency undermines the development and function of various IFN-γ-producing T cell subsets, thereby underlying TB.

• Autores: Arias Sierra, Andrés Augusto; Laurent, Abel; Al Ali, Fatima; Alkan, Gulsum; Ata, Manar; Béziat, Vivien; Bohlen, Jonathan; Boisson Dupuis, Stéphanie; Bustamante, Jacinta; Casavana, Jean Laurent; Chrabieh, Maya; Emiroğlu, Melike; Fieschi, Claire; Golec, Dominic P.; Hauck, Fabian; Han, Ji Eun; Jouanguy, Emmanuelle; Kaul, Zenia; Khan, Taushif; Kong, Xiao-Fei; Latour, Sylvain; Laine, Candice; Lei, Wei-Te; Martin, Emmanuel; Marr, Nico; Mansouri, Davood; Neven, Bénédicte; Ogishi, Masato; Pelham, Simon J; Parvaneh, Nima; Philippot, Quentin; Pekcan, Sevgi; Rodriguez, Rémy; Rozenberg, Flore; Rao, V Koneti; Schwartzberg, Pamela L.; Seeleuthner, Yoann; Tokgöz, Hüseyin; Uitto, Jouni; Vahidnezhad, Hassan; Yang, Rui; Youssefian, Leila
• Tipo de recurso: Article of investigation
• Fecha de publicación: 2023
• Institución: Universidad de Antioquia
• Repositorio: Repositorio UdeA
• Idioma: eng
• OAI Identifier: oai:bibliotecadigital.udea.edu.co:10495/40729
• Acceso en línea: https://hdl.handle.net/10495/40729
• Palabra clave: Interferon-gamma; Interferón gamma; Receptors, Antigen, T-Cell, alpha-beta; Receptores de Antígenos de Linfocitos T alfa-beta; Receptors, Antigen, T-Cell, gamma-delta; Receptores de Antígenos de Linfocitos T gamma-delta; T-Lymphocyte Subsets; Subgrupos de Linfocitos T; Thymus Gland; Timo; Tuberculosis; Tuberculosis; https://id.nlm.nih.gov/mesh/D007371; https://id.nlm.nih.gov/mesh/D016693; https://id.nlm.nih.gov/mesh/D016692; https://id.nlm.nih.gov/mesh/D016176; https://id.nlm.nih.gov/mesh/D013950; https://id.nlm.nih.gov/mesh/D014376
• Rights: openAccess
• License: http://creativecommons.org/licenses/by/2.5/co/